Refining stroke QTLs in recombinant inbred BXD mice

University Of Tennessee Health Sci Ctr, Memphis TN

Investigators

Abstract

Stroke remains a significant human disease, and understanding the genetic factors that contribute to its impact on specific individuals will ultimately be critical in targeting interventions. Although factors impacting the risk of stroke occurrence can be studied in human populations, those impacting stroke severity are best studied in experimental models. The BXD mouse strains are derived from parent B6 (C57BL/6) and D2 (DBA) lines, each BXD strain having defined contributions of parent gene sequence at different chromosomal loci. Preliminary data using previously available strains have identified novel quantitative trait loci (QTLs) impacting brain vulnerability to ischemic stroke, with a suggestion of sex- dependent variation in their effects. Strain number is the limiting factor in such analyses. The single aim of this study is to determine infarct volume following permanent focal ischemia for the 60 additional BXD strains that are now available. This expansion of the data set will maximize its power to map gene variants that modulate stroke outcome in these mice. The anticipated results will refine and potentially expand the set of newly identified stroke loci, defining potential candidate genes and molecular networks impacting stroke severity.